Vasoactive Intestinal Peptide: Evidence for a Hypothalamic Site of Action to Release Growth Hormone, Luteinizing Hormone, and Prolactin in Conscious Ovariectomized Rats*

Ovariectomized conscious rats bearing chronically implanted third ventricular cannula were injected with 2 μl 0.9% NaCl or 2 μd saline containing varying doses of vasoactive intestinal peptide (VIP), and plasma LH, PRL, GH, TSH, and FSH levels were measured by RIA in jugular blood samples drawn through an indwelling silastic cannula. Control injections of saline iv or into the third ventricle did not modify plasma hormone levels. Third ventricular injection of 4, 40, and 100 ng VIP produced a significant elevation within 5 min in plasma LH, while PRL levels were elevated only by 40- and 100-ng doses; however, the highest dose of 500 ng had no effect on plasma LH or PRL levels. Plasma GH titers increased significantly after third ventricular injection of each dose of VIP at 15 min and remained elevated for the duration of the experiment. Intravenous injection of VIP at doses of 40 and 1000 ng had no effect on plasma LH, but PRL levels were significantly elevated by the 1000-ng dose. Plasma GH was not odified by iv injection of 40 ng, while the 1000-ng dose induced a significant reduction. No significant changes in FSH or TSH levels were induced by third ventricular or iv injection of VIP. In vitro incubation of hemipituitaries with doses of VIP ranging from 10 ng to 10 μg had no effect on pituitary hormone release into the medium. Third ventricular injection of 100 ng VIP had no effect on blood pressure, while iv injection of 1000 ng significantly lowered blood pressure within 5–10 sec of injection. The results indicate that VIP can alter pituitary hormone release, presumably by a hypothalamic site of action, and are consistent with the concept that the peptide may act as a transmitter or modulator of neuronal activity controlling pituitary hormone release.